Independent, External, Blinded Retrospective Validation of an AI-based Prognostic Assay in ER-Positive/HER2-Negative Early Breast Cancer

This is an independent, external, blinded, retrospective validation study of a locked AI-based prognostic assay in ER-positive/HER2-negative EBC. The source population consists of eligible patients from ABCSG-8 with available archived tumor material suitable for H\&E slide digitization, with extended follow-up from ABCSG-16 where available. Primary analyses will be conducted in patients with slides that pass prespecified quality control and with required baseline clinicopathologic variables available or derivable according to the prespecified statistical analysis plan. The assay generates a continuous prognostic score and predefined risk categories using one digitized H\&E-stained surgical resection slide together with routine baseline clinicopathologic variables. Spotlight Medical will generate assay predictions while blinded to clinical outcomes. ABCSG will conduct the statistical analyses according to a prespecified protocol and statistical analysis plan. The primary objective is validation of the association of the assay with time to distant recurrence. Secondary objectives are validation of the association of the assay with disease-free survival and overall survival.